Carotenoids as referred to herein are a group of unsaturated hydrocarbons containing isoprene units or their derivatives substituted by various functional groups and the lipid addition compounds of the same.
It is well known that a healthy diet involves the consumption of appropriate amounts of high quality vegetables and fruits. Beside the different ingredients of these foodstuffs carotenoids are essential components for maintaining the health of the organism. Carotenoids, are highly efficient antioxidants, capturing the noxious free radicals continuously generated in the human organism. In addition, some carotenoids possess provitamin functions.
Beyond the provitamin function the main task of carotenoids is to inactivate the free radicals formed in increasing amounts in the human organism due to increased environmental hazards such as smoking, enhanced ultraviolet irradiation, air pollution, etc. However, even the best diet is unable to provide a sufficient continuous carotenoid supply which according to the data of various scientists may amount in the case of adults to a daily dose of 6-15 mg, so the need to apply carotenoid compositions as dietary supplements becomes ever more urgent.
Epidemiological surveys and other experimental data demonstrate that the incidence of morbidity and mortality due to various forms of cancer is lower in regions and in populations where vegetable and fruit consumption is high. The data show that this diet provides a sufficient carotenoid supply suggesting that carotenoids may have a prophylactic effect in preserving health.
As it is rather difficult, sometimes even impossible to provide a continuous carotenoid supply with the diet, there is an arising need to supplement the diet with carotenoid compositions prepared from various sources, and to ensure the required carotenoid supply in this way.
It has to be stressed that continuous carotenoid intake is a prerequisite of optimal efficacy. Free radicals are generated continuously in the organism thus they also have to be detoxicated continuously. This can only be achieved with a sufficient level of antioxidants in the organism. Carotenoids are not the only compounds which possess antioxidant properties, for example, tocopherols are also antioxidants. However, carotenoids are essential and together with tocopherols they even exert synergistic activity.
As a conclusion, carotenoids should be present in the human organism continuously and in suitable plasma levels to protect the organism prophylactically against abnormal processes induced by free radicals. As this effect is prophylactic, the regime has to be designed accordingly, i.e. the supplantation of the diet with carotenoids should be continuous.
Considering the above background the carotenoid compositions applied as continuous diet supplements, medications or eventually drugs (as vitamin preparations) should satisfy the following requirements:
a) the carotenoid spectrum should be similar to that of the human blood plasma, which is the following according to literature: PA1 b) the raw material used for preparing the composition should not represent any toxicological hazard, i.e. it cannot cause any nutritional health problem; PA1 c) the manufacturing process should be devised in a way to ensure that the final product excludes toxic contaminants (solvent residues for instance), as the composition will be used continuously; PA1 d) the composition should have sufficiently high active ingredient content to avoid administering large doses of the medication or dietary supplement accordingly the carotenoid concentration stated in point a) should be increased at least 10 to 100 fold. Consequently it is our aim to prepare a product with a concentration of 50,000-100,000 m/kg from carrots with a carotene content of 100-200 mg/kg. PA1 a) the carotenoid concentration is increased 400 to 500 fold compared to the carotenoid concentration of the raw material and two to fifteen fold compared to the carotenoid content of the crude chromoplast precipitate; PA1 b) the concentration is increased by cleaving the protein/lipid component of the lipoprotein complex and removing the salts of peptides, amino acids and fatty acids by dissolution from the side of carotenoids; PA1 c) the complex is cleaved by considering the solubilities of degradation products which are soluble at a rate several orders of magnitude higher in a water/alcohol (ethanol, rectified alcohol, isopropyl alcohol) mixture. Thus, no toxic solvent residues having an LD.sub.50 higher than that of ethanol are retained in the final product; PA1 d) the carotenoid spectrum of the product, obtained by processing chromoplasts isolated from appropriately selected raw materials, e.g. carrots or tomatoes, satisfies the general requirements, such as similarity to the carotenoid spectrum of the human blood plasma, in an optimal way. PA1 cellular elements of chromoplasts and chloroplasts are transferred into liquid phase (press-liquid, decanter-separator liquid) by mechanical processing partly performed in alkaline medium; PA1 chromoplasts in the liquid phase or in the suspension are denatured by adjusting the pH or by heat-treatment, or by the combination of both, and as a result they are precipitated from the liquid phase; PA1 the precipitated flocculi are separated (decantation, separation), the water soluble components are removed, and the carotenoid concentration in the separated flocculi is already significantly increased compared to the starting material; PA1 chromoplasts and chloroplasts containing the coloured substances, including the carotenoids, are lipoprotein complexes with a very high lipid content which holds the carotenoids (which are practically insoluble in water and poorly soluble even in organic solvents) in colloid solution, and transport them within the organism. A part of the lipids in the complex is retained in the product, and promotes the bioavailability of carotenoids. PA1 a) beta-carotene was assayed by the modified spectrophotometric Booth method M. A. van der Meer et al. (Wageningen), Z. Lebensmittel Unter-such. und Forschung, 185, 461-467 (1987)!;
______________________________________ alpha-carotene 0.12-0.15 .mu.mol/l, beta-carotene 0.40-0.80 .mu.mol/l, xanthophyll (lutein + zeaxanthine) 0.28-0.35 .mu.mol/l, lycopene 0.49-0.74 .mu.mol/l, ______________________________________
On the basis of the bioavailability of carotenoids to satisfy a daily carotenoid requirement of 10-15 mg/kg an adult would have to consume daily about 1 to 2 kg of carrots and tomatoes. Naturally this would induce adverse dietary side effects, such as excessive carbohydrate consumption, bad palatability and unbalanced complex diet. Furthermore, independently from the aforementioned aspects, to provide satisfactory carotenoid levels with adequate vegetable and fruit supplies would be limited by regional availability and financial constraints.
Summing up the aforementioned factors, the manufacturing and use of a suitable carotenoid composition would provide significant advantages.
The advantage of this invention should be appreciated if it is considered that the carotene content of prepared (processed or cooked) foods is rather low: 7,5-8,1 mg/100 g of alpha- and beta-carotene M. S. Micozzi et al., J. Nat. Cancer. Inst., 82, 282-285 (1990); and Heinonen et al., J. Agric. Food Chem., 37, 655-659 (1989)!, while that of the raw, uncooked carrot amounts to 150-200 mg/kg. Significant losses in carotene can be avoided with this new preparation which also has a much higher rate of absorption and bioavailability.